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  1. Davis TM, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, et al.
    J Intern Med, 1998 May;243(5):349-54.
    PMID: 9651556
    OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.

    DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min.

    SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years.

    MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations.

    RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment.

    CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

    Matched MeSH terms: Malaria, Vivax/blood
  2. Zhang R, Lee WC, Lau YL, Albrecht L, Lopes SC, Costa FT, et al.
    PLoS Negl Trop Dis, 2016 08;10(8):e0004912.
    PMID: 27509168 DOI: 10.1371/journal.pntd.0004912
    Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN) resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.
    Matched MeSH terms: Malaria, Vivax/blood
  3. Mak JW, Normaznah Y, Chiang GL
    Singapore Med J, 1992 Oct;33(5):452-4.
    PMID: 1455266
    The quantitative buffy coat (QBC) technique was compared with the conventional thick blood film technique in a malaria survey carried out in a mesoendemic area of malaria in Betau, Pahang, Malaysia. The QBC technique was found to be a rapid technique but had a sensitivity of about 56% and a specificity of 95%, using the thick blood film method as the "gold standard". Malaria species identification was unsatisfactory with the QBC technique as it could identify parasites correctly in only about 60% of specimens. It was unable to detect as positive about 58% of specimens which had parasite counts < or = 500 per ul but could detect about 94% of those with counts > 500 per ul. This difference in positive detection rate was significantly different (p < 0.05). It cannot quantify parasitemia easily and the specimens cannot be stored for future reference and for quality control purposes. It is therefore concluded that the QBC technique cannot replace the classical thick blood film technique for use in malaria control programmes. Its use may be appropriate in situations like busy blood banks and outpatient clinics where rapid screening of malaria infection is needed but where experienced malaria microscopists may not be available.
    Matched MeSH terms: Malaria, Vivax/blood
  4. Foo LC, Rekhraj V, Chiang GL, Mak JW
    Am J Trop Med Hyg, 1992 Sep;47(3):271-5.
    PMID: 1524139
    The malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of Malayan Aborigines matched for age, sex, proximity of residence to each other, and use of bed nets when sleeping in their jungle settlement in central Peninsular Malaysia. Malaria infection was determined from thick and thin Giemsa-stained blood films collected monthly for a period of six months. Blood films from ovalocytic individuals were found to be positive for malaria less often than in persons with normal red blood cells (P less than 0.05). Malaria infections per 100 person-months at risk were 9.7 in the ovalocytic group compared with 15.19 in the normocytic group. Among individuals parasitemic at any time, heavy infections (greater than or equal to 10,000 parasites/mm3 of blood) with Plasmodium falciparum, P. vivax, and P. malariae were encountered only in normocytic subjects, which comprised approximately 12.5% of the malaria-positive individuals in this group. In an earlier survey of 629 settlers that identified subjects for the above study, the prevalence of ovalocytosis was found to increase significantly with age. The above field observations support the view that ovalocytic individuals might have a survival advantage in the face of malaria. Consideration of the ovalocytic factor is indicated in future evaluations of malaria control measures in areas where ovalocytosis is prevalent.
    Matched MeSH terms: Malaria, Vivax/blood
  5. Odedra A, Webb L, Marquart L, Britton LJ, Chalon S, Moehrle JJ, et al.
    Am J Trop Med Hyg, 2020 11;103(5):1910-1917.
    PMID: 32815508 DOI: 10.4269/ajtmh.20-0491
    Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.
    Matched MeSH terms: Malaria, Vivax/blood
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